Considerations for Prescribing GLP-1s Get More Complicated

We know now that glucagon-like peptide 1 (GLP-1) drugs for obesity bring with them a whole host of other potential benefits, as well as a handful of side effects. But new research has brought a sharper focus on both the pros and the cons of these medications, and with that comes new challenges and opportunities for physicians to consider when prescribing them.

In a new study released this week in Nature Medicine, researchers studied four GLP-1 receptor agonist medications, namely, Ozempic, Zepbound, Mounjaro, and Wegovy, and identified175 possible health outcomes in 215,970 people on the medications. They then compared their health outcomes with those in 2.4 million individuals who were not on any weight loss medications.

Researchers found that outside of weight loss, patients experienced a laundry list of positive health outcomes, including a reduced risk for:

• Substance use disorders
• Suicidal ideation and schizophrenia
• Alzheimer’s disease and dementia
• Clotting disorders and infections
• Chronic obstructive pulmonary disease and liver diseases

A number of pathways seem to be working to make these drugs effective on some conditions seemingly unrelated to weight, said study author Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs St Louis Healthcare System.

For starters, obesity has negative implications for overall health, and by reducing obesity, you’re treating a number of problematic health outcomes. The other pathway is that GLP-1 receptors located all over the body in places like the brain are responsible for impulse control and reward signaling, which may be why the medications work to reduce substance use disorders. They’ve also been shown to reduce inflammation, thereby slowing neuro-inflammation, which has been linked to psychological disorders, including schizophrenia.

“These drugs are effective far beyond just being weight loss drugs, but they’re not without risks,” said Al-Aly.

The study also showed that along with positive outcomes, there were side effects, including an increased risk for nausea, vomiting, diarrhea, constipation, heartburn, gastroparesis, low blood pressure, fainting, sleep problems, headaches, kidney stones, kidney inflammation, and pancreatitis.

Medication Timing Is Key to Reducing Side Effects

Primary care doctors and obesity physicians should have an open dialogue with their patients from the start, consulting with them about things like medication timing, said Carolynn Francavilla, MD, a nationally recognized obesity physician who owns and operates Green Mountain Partners for Health and Colorado Weight Care, both in Denver.

When physicians prescribe these medications, they need to ensure their patients are aware of the possible side effects so that they’re not surprised and have a plan in place to deal with them, said Francavilla. Timing the dosage of their medication is important so that the side effects are the least problematic to their lifestyle.

The most common GLP-1 medications are once-weekly injections, and people tend to have the worse nausea and vomiting 36 hours after taking them. “Most of our patients choose to take the medication on a Friday or Saturday when those symptoms would be less disruptive to their work or other obligations,” said Francavilla.

Dosage and Food Choices Are Also Important

Dosage is another really important aspect of controlling side effects. The minimal recommended timing for one dose is about 4 weeks. “The two main goals of the medication are weight loss and diabetes management, so patients should stay on the lowest dosage possible until they feel like they’ve plateaued,” said Charu Sawhney, DO, MPH, an internal medicine physician with Harbor Health in Round Rock, Texas.

When patients move up on the dosage too fast, they’re going to have more trouble, said Sawhney. “This is when we see the most severe side effects like the malnutrition and dehydration that can sometimes land patients in the hospital,” she said.

Patients can also manage gastrointestinal side effects by avoiding certain food groups like heavy, fried, fatty foods which are slower to digest and alcohol which can make patients feel ill. “It’s the foods that we don’t want patients to eat anyway that they tend to become more sensitive to when they’re taking these medications,” said Sawhney.

And most importantly, when patients don’t feel as hungry, they’re less likely to drink enough water, which can cause a number of negative health outcomes, including kidney stones and kidney inflammation, said Sulagna Misra, MD, a primary care physician and founder of Misra Wellness in Los Angeles. “A lot of this can be alleviated just by making sure patients are properly hydrated,” she added.

Regular Check-Ins With Patients

Once patients are on these medications, their primary care physician or healthcare provider should be regularly checking in with them both to monitor their vitals and to check on their symptoms. It could mean an in-person or telehealth appointment, communication through a health portal, or a call, but in all cases, physicians need to be checking in and making sure their patients are on the correct dosage of the medication.

This might also mean medication adjustments, both for dosage of their GLP-1 and for other medications that the patient might be taking. One of the negative side effects is low blood pressure, which might be surprising to patients who had formerly been medicated for high blood pressure.

When patients lose significant weight, it’s not uncommon that their hypertension resolves itself, and when they’ve been previously medicated for high blood pressure, their medication can cause their blood pressure to go in the opposite direction, which means they might need either a lower dosage or to discontinue their high blood pressure medication.

“As patient’s metabolic disease improves, things like high blood pressure and diabetes may resolve themselves so we want to make sure we’re addressing that with their other medications,” said Francavilla.

But even in those who aren’t on high blood pressure medications, with large amounts of weight loss, some patients might still have low blood pressure, which can make them feel faintish when they stand up too quickly. Making sure that a patient is hydrated can also be helpful for dizziness caused by orthostatic hypotension, or low blood pressure, said Francavilla.

Some rare side effects, including pancreatitis, may result in the patient having to discontinue the use of GLP-1 medications for good. “In this case, your physician can prescribe an alternative such as a non–GLP-1 weight loss medication like Contrave, Qsymia, or Orlistat,” said Andres J. Acosta, MD, PhD, an associate professor of medicine and an expert on food intake regulation at the Mayo Clinic in Rochester, Minnesota.

In the end, the most important tool for serving patients taking GLP-1s is to know what they’re going through and be able to guide them along the way. “We have to know when a patient is suffering, and the more you meet with your patients, the more you’ll learn about both the side effects and also the positive health outcomes that they’re experiencing,” said Misra.